Article ; Online: A Novel Dual PI3K/mTOR Inhibitor, XIN-10, for the Treatment of Cancer.
International journal of molecular sciences
2023 Volume 24, Issue 19
Abstract: ... of research. The aim of this study was to explore the effect of XIN-10, a dual PI3K/mTOR ... inhibitor, on the growth as well as antiproliferation of tumor cells and to investigate the anti-tumor mechanism of XIN-10 ... From the AO staining, cell cycle and apoptosis, we found that XIN-10 had a more obvious inhibitory effect ...
| Abstract | An imbalance in PI3K/AKT/mTOR pathway signaling in humans often leads to cancer. Therefore, the investigation of anti-cancer medications that inhibit PI3K and mTOR has emerged as a significant area of research. The aim of this study was to explore the effect of XIN-10, a dual PI3K/mTOR inhibitor, on the growth as well as antiproliferation of tumor cells and to investigate the anti-tumor mechanism of XIN-10 by further exploration. We screened three cell lines for more in-depth exploration by MTT experiments. From the AO staining, cell cycle and apoptosis, we found that XIN-10 had a more obvious inhibitory effect on the MCF-7 breast cancer cell line and used this as a selection for more in-depth experiments. A series of in vitro and in vivo experiments showed that XIN-10 has superior antiproliferative activity compared with the positive drug GDC-0941. Meanwhile, through the results of protein blotting and PCR experiments, we concluded that XIN-10 can block the activation of the downstream pathway of mTOR by inhibiting the phosphorylation of AKT(S473) as well as having significant inhibitory effects on the gene exons of PI3K and mTOR. These results indicate that XIN-10 is a highly potent inhibitor with low toxicity and has a strong potential to be developed as a novel PI3Kα/mTOR dual inhibitor candidate for the treatment of positive breast cancer. |
|---|---|
| MeSH term(s) | Female ; Humans ; Apoptosis ; Breast Neoplasms/drug therapy ; Cell Line, Tumor ; Cell Proliferation ; MTOR Inhibitors/pharmacology ; MTOR Inhibitors/therapeutic use ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide-3 Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins c-akt/metabolism ; TOR Serine-Threonine Kinases/metabolism |
| Chemical Substances | MTOR Inhibitors ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Phosphoinositide-3 Kinase Inhibitors ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1) |
| Language | English |
| Publishing date | 2023-10-01 |
| Publishing country | Switzerland |
| Document type | Journal Article |
| ZDB-ID | 2019364-6 |
| ISSN | 1422-0067 ; 1422-0067 ; 1661-6596 |
| ISSN (online) | 1422-0067 |
| ISSN | 1422-0067 ; 1661-6596 |
| DOI | 10.3390/ijms241914821 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.